Behavioral Epigenetics and the NICU

Evi Dewhurst

A recent article on behavioral epigenetics made me wonder how it could impact patients in the NICU, and what could be done to offset consequences of painful or stressful experiences. It all happened on the way to NICU Leadership Forum.

As I waited for my plane to Arizona for NICU Leadership Forum a few weeks ago, I realized I was missing airplane essentials: water, snacks and reading material. Fortunately, after selecting refreshment and a suitably calorie-laden snack, my hands did not pick up the latest entertainment rag or beauty bonanza issue to read. Purely on impulse, my fingers plucked the most recent issue of Discover magazine from the newsstand.

Feeling a bit bemused by my intellectual choice, I settled in thirty minutes later for the short plane ride with water at hand, Skittles package opened and magazine propped on the tray. An attention-grabbing article in the issue revealed itself quickly, titled “Trait or Fate,” written by Dan Hurley. The author opened his article with the words, “Darwin and Freud walk into a bar.” With my education background in psychology, he had me at Freud! Over the course of several pages he covered research demonstrating how life experience can alter you, physically and behaviorally.

What follows here is an extreme blog version of article synopsis, and closed by the answer to what you’ll be asking yourself in about three minutes. “What does all this have to do with neonatal health?”

Keep these definitions handy, as you’ll need them in a minute:

Epigenetics: the study of the chemical modification of specific genes or gene-associated proteins of an organism.1

Methyl Group: one of the most common structural units of organic compounds, consisting of three hydrogen atoms bonded to a carbon atom, which is linked to the remainder of the molecule.2

A Brief Introduction:

Spools of DNA inside a cell’s nucleus need something specific to tell them which genes to transcribe. It could be something like a heart cell, for example. Enter the methyl group. Methyl groups develop due to certain chemical exposure or even diet.  They can influence certain genes by selecting and attaching to the DNA within each cell. They locate themselves beside, yet separate, from the double-helix DNA code. It is this influence which epigenetics studies, and thus the reason for the name, since “epi” is Greek for over, outer, above.

In the Beginning:

Early on, researchers believed epigenetic changes occurred only during fetal development. Later it was proven not to be the case. Molecular changes to the DNA could and do get added into adulthood. These can cause a rash of cellular changes, even leading to disease. Researchers knew methyl groups could attach as a result of diet or chemical exposure, but the biggest surprise was truly unexpected: Epigenetic change could be hereditary. These methyl group back-seat drivers to DNA could actually be passed from generation to generation.

A Fortuitous Meeting:

Enter Moshe Szyf, a molecular biologist and geneticist at McGill University in Montreal, and Michael Meaney, a McGill neurobiologist. By chance they happened to attend the same 1992 international meeting in Spain and crossed paths in Madrid. A conversation sprang up that eventually led to their desire to solve a pertinent question. Could epigenetic changes occur as a result of life experiences? This would eventually become a whole new field of study known as behavioral epigenetics.

Behavioral Epigenetics: the field of study examining the role of epigenetics in shaping animal (including human) behavior. Epigenetic gene regulation involves changes other than to the sequence of DNA and includes changes to histones (proteins around which DNA is wrapped) and DNA methylation. These epigenetic changes can influence the growth of neurons in the developing brain as well as modify activity of the neurons in the adult brain. Together, these epigenetic changes on neuron structure and function can have a marked influence on an organism’s behavior.3

Molecular scars left behind on DNA after an individual endured traumatic life experience appeared to actually influence behavior. And ultimately, trauma endured by recent ancestors could be passed down genetically, as epigenetic changes are hereditary.

A Test of Rats and Stress:

Szyf and Meaney eventually performed a series of rat studies, closely monitoring mothering skills and direct results to the hippocampus of the brain in their pups (the hippocampus regulates stress response). With inattentive mothers, pups had “highly methylated glucocorticoid receptor production” (glucocorticoid receptors regulate sensitivity to stress hormones), which resulted in insufficient receptors. The pups grew up to be anxious and stressed individuals. With attentive mothers, the genes for the glucocorticoid receptors were rarely methylated.

To verify they were on the right track, they performed additional testing and switched the pups at birth. The pups born to attentive mothers were raised by the inattentive mothers. The pups ultimately had the “same outcome as genetic offspring raised in the same environment.” This further supported their hypothesis of behavioral epigenetics shaping behavior, for good and for bad. The article continued to describe later rat-based studies conducted by these two, including the idea that a direct dose of trichostatin A to the hippocampus can remove methyl groups, causing the epigenetic changes to disappear. It opened a whole new window: could a wonder drug be created to cleanse unwanted methyl groups?

And Finally:

Meanwhile, other researchers conducted human studies to verify experiences as a child will “affect the epigenome of the brain and result in emotional tendencies more strongly” than experiences as an adult. This applies to negative and positive experiences, not only for the individual, but from their own hereditary gene pool as well. The men and women who have built their careers in epigenetics and behavioral epigenetics have pursued their passion and research for many years, leading to information that can advance our understanding of physical and psychological health.

At Last, Relevance:

While I feel all this information is stimulating, I must finally arrive at the question of the day. How does this relate to the NICU and neonatal health?

Infants in the NICU experience many traumatic events during their stay. Clearly they are at a health disadvantage, which is a trauma all its own. From there these babies undergo day-to-day treatments, all of which are done with the best intentions to encourage improved overall health. While the intent is certainly justified, the experiences are unfortunately stressful. Does the stress of patient experience have a physical and psychological impact? As epigenetics and behavioral epigenetics show, the answer is yes. However, as mentioned, negative and positive experience can affect the methyl groups developing beside the DNA, which shape future behavior and health of these tiny individuals.

Day-to-day environmental factors such a dim lights, soothing sounds and familiar voices bring comfort. Being held by a parent, family member or caring nurse lowers the heart rate and stress levels. A soft touch, a beloved pacifier or even the smell of something familiar can all be restful, beautiful experiences to a NICU patient whose world is so small. A warm feed, everyday routine, or a bit of gentle music could be the right sensory experience to encourage a feeling of security. Just as these patients in your care are tiny, the impact of small bits of peace and joy can create a larger sense of comfort and contentment, offsetting the stress they must endure on the road to health.

If you find yourself concerned about stressful experiences NICU babies must endure, think of the many positive efforts you can do for them that will make all the difference in keeping pesky methyl groups at bay and help your beloved charges grow strong and healthy, in mind and in body.

“Life is made up, not of great sacrifices or duties, but of little things,
in which smiles and kindness, and small obligations given habitually,
are what preserve the heart and secure comfort.”

– Humphrey Davies4


Looking for additional reading on this topic?
View Sandy Beauman’s related blog entry, Painful Experiences.



Dan Hurley, “Trait or Fate,” Discover 05 (2013): 48-55